Whitehead Institute for Biomedical Research
Professor of Biology, Massachusetts Institute of Technology
The origin of aggressive breast cancers can be traced to a change that breast cancer cells undergo as they evolve from a more benign to a more malignant, aggressive state. This change, termed the epithelial-mesenchymal transition (EMT), confers on them traits such as movement, invasiveness, a resistance to therapy, and an ability to generate more copies of themselves – the last trait associated with the behavior of cancer stem cells. Such cells, which serve as the pioneers of new metastases, must be eradicated in order to prevent the delayed relapses that threaten many women who are initially treated and ostensibly cured of breast cancer. Dr. Weinberg's team researches the origins of these cancer stem cells and how their development may be prevented within tumors.
Dr. Weinberg’s team is studying the conversion of relatively benign breast cancer cells into ones that are capable of invasion and metastasis. Breast cancers, like all carcinomas, derive from the conversion of normal epithelial tissues in tumors that grow autonomously and no longer respect the requirements of the normal tissues in which they arose. These researchers are studying the changes in epithelial cells in the normal mouse and human mammary gland in order to understand how these cells acquire aggressive traits, notably those leading to life-threatening metastases. This acquisition often, and perhaps invariably, depends on a cell-biological program that is hard-wired into epithelial cells and is normally not expressed. However, in advanced carcinoma cells, activation of this program, termed the epithelial-mesenchymal transition (EMT) enables carcinoma cells to concomitantly acquire an entire suite of traits that enable them, in turn, to generate highly aggressive malignancies. Often, and perhaps invariably, activation of the EMT program in breast cancer cells derives from signals that they receive from the nearby “tumor stroma” – the collection of normal cells that were previously recruited into the tumor, initially in order to support the ongoing growth and viability of the carcinoma cells. Over the past year the researchers have focused largely on the molecular machinery that enables breast carcinoma cells to respond to these stromal signals and activate their endogenous EMT programs, thereby empowering these cells to spawn the metastases that are responsible for essentially all human breast cancer-associated deaths.
Dr. Weinberg is a founding member of the Whitehead Institute for Biomedical Research and the Daniel K. Ludwig Professor for Cancer Research at the Massachusetts Institute of Technology (MIT). He is also the first Director of the Ludwig Cancer Center at MIT. He is an internationally recognized authority on the genetic basis of human cancer.
Dr. Weinberg and his colleagues isolated the first human cancer-causing gene, the ras oncogene, and the first known tumor suppressor gene, Rb, the retinoblastoma gene. The principal goal of his research program is to determine how oncogenes, their normal counterparts (proto-oncogenes), and tumor suppressor genes fit together in the complex circuitry that controls cell growth. More recently, his group has succeeded in creating the first genetically defined human cancer cells. He is particularly interested in applying this knowledge to improve the diagnosis and treatment of breast cancer.
Dr. Weinberg is the author or editor of six books and more than 350 articles. He has written a comprehensive cancer textbook entitled The Biology of Cancer. His other books, intended for a lay audience, are One Renegade Cell, Racing to the Beginning of the Road: The Search for the Origin of Cancer and Genes and the Biology of Cancer, co-authored with Dr. Harold E. Varmus, former Director of the National Institutes of Health. He is an elected Member of the U.S. National Academy of Sciences and Fellow of the American Academy of Arts and Sciences. He is a Member of the American Philosophical Society and the Institute of Medicine.
Among Dr. Weinberg's many honors and awards are the Discover Magazine 1982 Scientist of the Year, the National Academy of Sciences/U.S. Steel Foundation Award in Molecular Biology, the Sloan Prize of the General Motors Cancer Research Foundation, the Bristol-Myers Award for Distinguished Achievement in Cancer Research, the Harvey Prize from the American Society for Technion Israel Institute of Technology, the Gairdner Foundation International Award, the Keio Medical Foundation Prize, the 1997 National Medal of Science, the City of Medicine Award and the 2004 Wolf Foundation Prize and the Prince of Asturias Science Prize. He has served on scientific advisory boards for the Institute of Molecular Pathology in Vienna, Austria, the Weizmann Institute in Rehovot, Israel, and the Massachusetts General Hospital in Boston.
Born in Pittsburgh in 1942, Dr. Weinberg received his BS (1964) and PhD (1969) degrees in Biology from MIT. He did postdoctoral research at the Weizmann Institute and the Salk Institute in La Jolla, California, and then returned to MIT in 1972. In 1982, he was appointed Professor of Biology at MIT.